ABSTRACT Although more than 75% of women who smoke want to quit, they do not have the same success that men have. This is of particular concern as premenopausal women smokers are more likely to experience smoking- related morbidity and mortality than men smokers. Further, mothers are the primary source of secondhand smoke exposure in children. Quitlines are broad reaching, cost-effective programs that disseminate smoking cessation treatment; however, little research has focused on tailoring quitline programs for women. The goal of this study is to investigate the feasibility and preliminary efficacy of an innovative quitline-based intervention that times premenopausal female smokers' quit attempts to their menstrual cycle. Emerging evidence indicates the follicular phase (two weeks post onset of menses) is associated with increased efficacy of nicotine replacement therapy (NRT) for smoking cessation as compared to the luteal phase (two weeks prior to menses onset). Thus, timing cessation interventions based on menstrual phase has potential to improve quit rates among women, a group of smokers at high-risk for relapse. This study will enroll 116 women between 18-40 years of age from the Arizona Smokers' Helpline. Participants will be randomized to the follicular phase group (quit date set six to eight days post onset of menses) or standard care control (quit date three weeks after enrollment, regardless of menstrual phase, which is standard quitline practice). Menstrual phase identification will be determined using methods from published recommendations. Consistent with existing quitline protocols, participants will receive 4-weeks of NRT (patch) concurrent with six-weeks of telephone-based behavioral coaching. Data will be collected at Baseline, Week 0 (quit day), Week 1, Week 4 (end of treatment), and a follow-up at Month 3 using telephone interviews, validated questionnaires, and dried blood spots (to measure sex hormones to verify menstrual phase and cotinine to verify smoking status). Primary outcomes include determining acceptability and feasibility of this menstrual-cycle based intervention (recruitment and retention rate, the ability to correctly identify the menstrual phase, and overall participant study satisfaction). Smoking cessation outcomes (self-report and/or biochemically verified) will be assessed at Week 1, Week 4 (end of treatment), and at Month 3 follow-up. Finally, we will explore menstrual phase differences in theoretically- relevant factors known to be associated with smoking cessation (e.g., social support, weight concerns, urge coping). Study results will guide protocol development and generate hypotheses for larger-scaled randomized controlled trials. This study is novel and pragmatic, integrating emerging evidence for the role of menstrual- cycle timed quit dates with state-of-the-science quitline cessation programs. If successful, this model can be cost-effectively replicated within state and national quitline programs. It can address the unique barriers to smoking behavior change among premenopausal women, increase successful quit outcomes and reduce disease risk associated with high tobacco-related morbidity rates.